ABSTRACT
BACKGROUND
: Patients are usually maintained on at least two immunosuppressive drugs (ISDs) after
the first year post-heart transplant. Anecdotally, some children are switched to single-drug
monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated
with differences in immunosuppression after heart transplantation are unknown for
children.
OBJECTIVES
: A priori we defined a non-inferiority hypothesis for monotherapy compared to ≥2 ISDs. The
primary outcome was graft failure, a composite of death and retransplantation. Secondary
outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy
and dialysis.
METHODS
: This international, multicenter, retrospective, observational cohort study used
data from the Pediatric Heart Transplant Society. We included patients who underwent
first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of
follow-up data available.
RESULTS
: Our analysis included 3,493 patients with a median time post-transplant of 6.7 years.
There were 893 patients (25.6%) switched to monotherapy at least once with the remaining
2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year
post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio
(HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p=0.002).
There were no meaningful differences in the incidence of secondary outcomes between
groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy
(HR 0.58, 95%CI: 0.45-0.74).
CONCLUSIONS
: For pediatric heart transplant recipients placed on monotherapy, immunosuppression
with a single ISD after the first year post-transplant was non-inferior to standard
therapy with ≥2 ISDs in the medium term.
CONDENSED ABSTRACT
: Some children are switched to a single immunosuppressive drug (ISD) for various
reasons after heart transplant, but outcomes associated with differences in immunosuppression
are unknown for children. We assessed graft failure in children on a single ISD (monotherapy)
compared to ≥2 ISDs in a cohort of 3,493 children with a first heart transplant. We
found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We
concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression
with a single ISD after the first year post-transplant was non-inferior to standard
therapy with ≥2 ISDs in the medium term.
KEY WORDS
Abbreviations:
HT (heart transplantation), ISD (immunosuppressive drug), PTSD (post-transplant lymphoproliferative disease), PHTS (Pediatric Heart Transplant Society), CAV (coronary artery vasculopathy), MMF (mycophenolate Mofetil)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
REFERENCES
- Immunosuppressive drugs after solid organ transplantation.The Netherlands journal of medicine. 2013; 71: 281-289
- Immunosuppression Therapy for Pediatric Heart Transplantation.Current Treatment Options in Cardiovascular Medicine. 2010; 12: 489-502
- Current status of immunosuppressive agents for solid organ transplantation in children.Pediatr Transplant. 2012; 16: 106-122
- The Registry of the International Society for Heart and Lung Transplantation: Eighteenth Official Pediatric Heart Transplantation Report–2015; Focus Theme: Early Graft Failure.J Heart Lung Transplant. 2015; 34: 1233-1243
- International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy—2010.The Journal of Heart and Lung Transplantation. 2010; 29: 717-727
- The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.PLoS Med. 2007; 4: e296
- B cells mediate chronic allograft rejection independently of antibody production.J Clin Invest. 2014; 124: 1052-1056
- Cardiac allograft vasculopathy after heart transplantation: Pathophysiology, detection approaches, prevention, and treatment management.Trends Cardiovasc Med. 2021;
- Predictors of cardiac allograft vasculopathy in pediatric heart transplant recipients.Pediatr Transplant. 2013; 17: 436-440
- Pediatric recipient survival beyond 15 post-heart transplant years: a single-center experience.Ann Thorac Surg. 2014; 98 (discussion 2150-1): 2145-2150
- Risk Factors for Survival After Heart Transplantation in Children and Young Adults: A 22-Year Study of 179 Transplants.World J Pediatr Congenit Heart Surg. 2018; 9: 557-564
- Trends in the indications and survival in pediatric heart transplants: a 24-year single-center experience in 307 patients.Ann Thorac Surg. 2012; 94 (discussion 815-6): 807-815
- Pediatric heart transplantation: 23-year single-center experience.Eur J Cardiothorac Surg. 2011; 39: e83-e89
- Cause of death in pediatric and infant heart transplant recipients: review of a 20-year, single-institution cohort.J Heart Lung Transplant. 2009; 28: 579-584
- Long-term results of tacrolimus monotherapy in cardiac transplant recipients.J Heart Lung Transplant. 2006; 25: 699-706
- Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial).J Heart Lung Transplant. 2007; 26: 992-997
- A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.Circ Heart Fail. 2011; 4: 129-137
- Quest for lower immunosuppression in cardiac transplantation: an analysis of the TICTAC trial.Future Cardiol. 2011; 7: 293-297
- Strategies in immunosuppression after heart transplantation: is less better?.Circ Heart Fail. 2011; 4: 111-113
- Impact of tacrolimus variability on pediatric heart transplant outcomes.Pediatr Transplant. 2021; : e14043
- The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients.Transplantation. 2016; 100: 39-53
- Regulation of anti-HLA antibody-dependent natural killer cell activation by immunosuppressive agents.Transplantation. 2014; 97: 294-300
- The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-second pediatric heart transplantation report - 2019; Focus theme: Donor and recipient size match.J Heart Lung Transplant. 2019; 38: 1028-1041
- The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult lung and heart-lung transplantation Report-2019; Focus theme: Donor and recipient size match.J Heart Lung Transplant. 2019; 38: 1042-1055
- Results with cyclosporine monotherapy in long-term cardiac transplant recipients.Transplant Proc. 2010; 42: 1291-1293
- Cyclosporine monotherapy in cardiac transplantation: review of the literature.Transplant Rev (Orlando). 2011; 25: 131-135
- Efficacy of immunosuppression monotherapy after liver transplantation: a meta-analysis.World J Gastroenterol. 2014; 20: 12330-12340
- Calcineurin inhibitor- and corticosteroid-free immunosuppression in pediatric heart transplant patients.Pediatr Transplant. 2017; 21
- Long-term experience using CNI-free immunosuppression in selected paediatric heart transplant recipients.Pediatr Transplant. 2021; : e14111
- Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients.J Am Coll Cardiol. 2018; 71: 636-650
- Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study.Lancet. 2006; 367: 233-239
- Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients.Pediatr Transplant. 2009; 13: 54-62
Article info
Publication history
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.
